Pubertal Timing and Growth Dynamics in Children With Severe Primary IGF-1 Deficiency: Results From the European Increlex

BACKGROUND

Puberty is delayed in untreated children and adolescents with severe primary IGF-1 deficiency (SPIGFD); to date, it has not been reported whether recombinant human insulin-like growth factor-1 mecasermin (rhIGF-1) treatment affects this. Pubertal growth outcomes were extracted from the European Increlex

METHODS

The Eu-IGFD Registry includes children and adolescents aged 2 to 18 years with growth failure associated with SPIGFD who are treated with rhIGF-1. Reported outcomes include: age at last registration of Tanner stage 1 and first registration of Tanner stage 2-5 (T2-T5; based on breast development for girls and genital development for boys, respectively); maximum height velocity during each Tanner stage; and pubertal peak height velocity (PPHV). Data cut-off was 13 May 2019.

RESULTS

This analysis included 213 patients (132 boys and 81 girls). Mean (SD) age at last registration of T1 and first registration of T5 was 13.0 (2.0) and 16.3 (1.6) years, respectively, in boys and 11.6 (1.8) and 14.7 (1.5) years, respectively, in girls. Among patients reaching the end of puberty (25 boys and 11 girls), mean (SD) height SDS increased from -3.7 (1.4) at baseline in the Eu-IGFD Registry to -2.6 (1.4) at T5 in boys and from -3.1 (1.1) to -2.3 (1.5) in girls. Maximum height velocity was observed during T2 in girls and T3 in boys. Median (range) PPHV was 8.0 (0.3-13.0) cm/year in boys and 6.8 (1.3-9.6) cm/year in girls and occurred most frequently during T2. Overall, the adverse events seen in this analysis were in line with the known safety profile of rhIGF-1.

CONCLUSION

Children and adolescents treated with rhIGF-1 for SPIGFD with growth failure experienced an increase in height SDS in prepubertal years compared with baseline. Despite 1.5 years delay in pubertal start and a delayed and slightly lower PPHV, height SDS gain during puberty was maintained.

Informations de copyright

Copyright © 2022 Bang, Polak, Perrot, Sert, Shaikh and Woelfle.

Déclaration de conflit d'intérêts

PB has attended advisory boards and received board of directors fees from Ipsen and Lilly, and has received consulting fees from Ipsen, Sandoz, Pfizer, Lilly and Versatis. JW has attended advisory boards and received board of directors fees from Ipsen and Novo Nordisk, and has received corporate-sponsored research fees from Pfizer and Ipsen, as well as speaker fees from Merck-Serono, Hexal, Pfizer and Novo Nordisk. MP has attended advisory boards and received board of directors fees from Ipsen (Increlex Registry), Novo Nordisk (Global Norditropin Advisory board), Pfizer France, and has received corporate-sponsored research fees from Ipsen, Novo Nordisk, Pfizer, Sandoz, Merck and Sanofi, as well as speaker fees from Novo Nordisk and Ipsen. VP and CS are both employees of Ipsen. The authors declare that this study received funding from Ipsen. The funder contributed to the study design, data collection and analysis, decision to publish, and funded editorial support for preparation of the manuscript.